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nephrogenic diabetes insipidus (NDI)

Etiology: 1) acquired tubulointerstitial disease a) pyelonephritis b) analgesic nephropathy c) multiple myeloma d) amyloidosis e) obstructive uropathy f) sarcoidosis g) hypercalcemia h) severe hypokalemia i) Sjogren's syndrome j) sickle cell disease k) cystinosis l) nephronophthisis m) renal transplantation 2) drugs or toxins a) lithium carbonate b) demeclocycline c) amphotericin B d) propoxyphene e) methoxyflurane f) foscarnet g) ethanol h) diphenylhydantoin i) ifosfamide j) cidofovir k) didanosine l) ofloxacin 3) congenital anomalies a) hereditary nephrogenic diabetes insipidus b) polycystic or medullary cystic renal disease 4) 3rd trimester of pregnancy (rare) - vasopressinase production by placenta resulting in catabolism of vasopressin [2] Pathology: -> complete or partial resistance of antidiuretic hormone (ADH) or vasopressin &/or impairment of the counter-current mechanism in the loop of Henle Genetics: - X-linked form associated with defects in AVPR2 - type 2 (autosomal) associated with defects in AQP2 Clinical manifestations: - polyuria, polydipsia, nocturia Laboratory: 1) urine concentrating deficit is not severe 2) urine osmolality - < 300 mosm/kg 3) 24 hour urine - volumes of 2-3 L/day, as high as 6 liters/day 4) urine concentrating test a) urine osmolality does not increase after water deprivation b) urine osmolality does NOT increase 60 minutes after administration of 5 units subcutaneous arginine vasopressin 5) ADH in plasma is normal or high 6) serum sodium generally normal Radiology: - renal ultrasound Differential diagnosis: psychogenic polydipsea: low normal serum sodium to hyponatremia Management: 1) unresponsive to vasopressin (dDAVP) 2) most cases have treatable cause 3) general measures (see diabetes insipidus) - thiazide diuretics & dietary salt restriction (not drug induced) - indomethacin may be used in combination [5] 4) discontinue offending medications - Li+ 1] if Li+ must be continued, use with amiloride a] amiloride blocks uptake of Li+ by the distal tubule b] mild extracellular fluid volume contraction c] increased Na+ & H2O absorption at the proximal tubule d] decreased urine volume 2] volume depletion induced by diuretics may increase proximal tubule resorption of Na+ & Li+, & increase Li+ concentration 5) correct hypokalemia 6) correct hypercalcemia

Interactions

disease interactions

Related

amyloidosis chronic interstitial nephritis (analgesic nephropathy, drug-induced chronic interstitial nephritis) hypercalcemia hypokalemia multiple myeloma; plasmacytoma/plasma cell myeloma postrenal azotemia; obstructive uropathy pyelonephritis renal transplantation sarcoidosis sickle cell (hemoglobin SS) disease Sjogren's syndrome (autoimmune epitheliitis)

General

diabetes insipidus (DI) kidney disease; renal disease

Database Correlations

OMIM correlations

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 50-51
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015
  3. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 239, 1324
  4. Grunfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol. 2009 May;5(5):270-6 PMID: 19384328
  5. Bedford JJ, Weggery S, Ellis G et al Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. Clin J Am Soc Nephrol. 2008 Sep;3(5):1324-31. PMID: 18596116 Free PMC Article
  6. Christensen BM, Zuber AM, Loffing J et al alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. J Am Soc Nephrol. 2011 Feb;22(2):253-61. PMID: 21051735 Free PMC Article
  7. Feldman BJ, Rosenthal SM, Vargas GA et al Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med. 2005 May 5;352(18):1884-90. PMID: 15872203 Free Article
  8. Devuyst O. Physiopathology and diagnosis of nephrogenic diabetes insipidus. Ann Endocrinol (Paris). 2012 Apr;73(2):128-9. Review. PMID: 22503803
  9. NEJM Knowledge+ - Sands JM, Bichet DG; Nephrogenic diabetes insipidus. Ann Intern Med. 2006 Feb 7;144(3):186-94. PMID: 16461963 Review.
  10. MedlinePlus: Diabetes insipidus - neprogenic http://www.nlm.nih.gov/medlineplus/ency/article/000511.htm